Phthalylglycine aldehyde → tert-butyl(2S)-2-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]amino}-3,3-dimethylbutanoate

Participants

Reaction Conditions

Reaction Steps

A solution of the product of Example 111-1 (46.5 g, 246.0 mmol) in tetrahydrofuran (900 mL) was treated with L-tert-leucine-t-butyl ester hydrochloride salt (66.1 g, 295.2 mmol, 1.2 equivalents) stirred at 20° C. for 2 hours, treated with sodium triacetoxyborohydrodride (78.2 g, 369.0 mmol, 1.5 equivalents) portionwise over 5 minutes (slightly exothermic), stirred at 20° C. for 2 hours, diluted with ethyl acetate (1 L) and washed with water (1 L). The organic layer was washed with water (1 L), 10% NaHCO3 (2×1 L) and brine (1 L). The organic layer was dried over MgSO4, filtered, and concentrated to afford the title compound (87 g, 98.2% yield). 1H NMR (CDCl3): δ 7.82 (m, 2 H), 7.70 (m, 2 H), 3.77 (t, 2 H), 2.92 (m, 1 H), 2.73(s, 1H), 2.68(m, 1H), 1.44(s, 9H), 0.86(s, 9H).

Provenance & Evidence